Endocan is a novel endothelium derived soluble dermatan sulfate proteoglycan. It has the property of binding to a wide range of bioactive molecules associated with cellular signaling and adhesion and thus regulating proliferation, differentiation, migration, and adhesion of different cell types in health and disease. An increase in tissue expression or serum level of endocan reflects endothelial activation and neovascularization which are prominent pathophysiological changes associated with inflammation and tumor progression. Consequently, endocan has been used as a blood-based and tissue-based biomarker for various cancers and inflammation and has shown promising results.

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Objectives: To explore the protective effect of progesterone on inflammation and oxidative stress in a rat model of sepsis created by cecal ligation and puncture (CLP). Materials and Methods: Rats were randomly divided into 4 groups: Overiectomy group (OVX), sham operated (control), sepsis (CLP) group and progesterone-treated CLP group (CLP+ progesterone). The rats in CLP+ progesterone group received intraperitoneal progesterone (2 mg/kg). Cardiac blood samples were obtained for the measurement levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Tissue samples, including liver, kidney and uterus of rats were prepared to determine activities of myeloperoxidase (MPO), glutathione peroxidase (GPx) and levels of malondialdehyde (MDA). Results: Increased serum IL-6 and TNF-α levels were found in the CLP group in comparison with the control group (P = 0.01, P = 0.02; respectively). In CLP+ progesterone group, mean MDA concentration of kidney tissue was significantly lower than in CLP group (P = 0.003). Liver MDA concentration of the CLP+ progesterone group was not significantly different from that of the control group. While there were no significant differences among groups regarding liver MPO; in the CLP group, MPO activity in kidney (P = 0.02) and uterine tissues (P = 0.03) were found to be significantly higher compared to the control group. In CLP+ progesterone group, mean MPO activities of all tissues were not different than those of control group. The uterine tissue GPx activity in the CLP+ progesterone group was not statistically significantly different from control group. Conclusions: We suggest that progesterone ameliorates sepsis syndrome by reduction of the inflammatory cytokines IL-6 and TNF-α, and by restoration of antioxidant enzyme activities in some tissues.

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Objectives: This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with metformin on streptozotocin (STZ)-nicotinamide-induced diabetic nephropathy (DN). Materials and Methods: Type 2 diabetes in rats was induced with STZ-nicotinamide. The diabetic rats were treated with coenzyme Q10 (10 mg/kg, p.o.) alone or coenzyme Q10 + metformin. Various parameters of renal function tests such as serum creatinine, urea, uric acid, and markers of oxidative stress such as renal malondialdehyde (MDA) level, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) activity, transforming growth factor-β (TGF-β), and nitrite content were estimated in renal tissues. All treated animal were subjected to histopathological changes of kidney. Result: Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum urea, serum creatinine, uric acid. In addition, STZ-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and glutathione (GSH) level. Moreover, TNF-α, MPO activity, TGF-β, and nitrite content were significantly increased in diabetic rats, while treatment with coenzyme Q10 or metformin or their combination ameliorate STZ-nicotinamide induced renal damage due to improvement in renal function, oxidative stress, suppression of TNF-α, MPO activity, TGF-β and nitrite content along with histopathological changes. Conclusions: This finding suggests that the treatment with coenzyme Q10 or metformin showed significant renoprotective effect against STZ-nicotinamide-induced DN. However, concomitant administration of both showed a better renoprotective effect than coenzyme Q10 or metformin alone treatment.

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Objectives: This study explores the mechanism of tanshinone IIA (TSN)-mediated inhibition of myocardial fibrosis by investigating the effect of TSN on transforming growth factor β1 (TGFβ1) signal transduction in rat cardiac fibroblasts (CFs). Materials and Methods: CFs were isolated from neonatal Sprague-Dawley rats by trypsin digestion and differential adhesion and stimulated with 5 ng/mL TGFβ1 and TSN (10⁻⁶ , 10⁻⁵ , or 10⁻⁴ mol/L). The expression of fibronectin (FN) mRNA in the CFs was determined using reverse transcriptase-polymerase chain reaction and the protein expression of FN and Smads in CFs was detected using Western blot. The intracellular expression and localization of Smads in the CFs were analyzed using immunocytochemistry. Results: TGFβ1 induced the expression of FN and Smads in a time-dependent manner. At the end of the culture treatment, the mRNA expression of FN and the expression of phosphorylated Smad2/3 (p-Smad2/3) increased significantly (P < 0.01). TSN pretreatment (10⁻⁵ and 10⁻⁴ mol/L) reduced the expression of FN and p-Smad2/3 (P < 0.01) following TGFβ1 stimulation and led to a significant decrease in the nuclear staining intensity and a positive rate of p-Smad2/3 (P < 0.05 and P < 0.01, respectively). Conclusion: The inhibitory effect of TSN on myocardial fibrosis may be associated with its inhibition of TGFβ1-induced Smad2/3 phosphorylation and p-Smad2/3 nuclear translocation, which blocks the TGFβ1/Smad signaling pathway in CFs.

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Black hairy tongue (BHT) also called as lingua villosa nigra, is a self limiting benign condition characterized by hypertrophy and elongation of filiform papillae of tongue with brown or black discoloration. Smoking, poor oral hygiene, xerostomia, using peroxide containing mouth washes, substance abuse and drugs (steroids, methyldopa, olanzapine, etc) are the predisposing factors. However its occurrence in relation to linezolid ingestion among south Indians has not been reported in PubMed database. Here we report a case, where significant association of linezolid intake with BHT was found in a 10-year-old boy, who was treated with tablet linezolid for post surgical infection of left side radial neck fracture. This case is reported for the rarity of occurrence with linezolid therapy. According to Naranjo adverse drug reaction (ADR) causality scale, the association of BHT due to linezolid in our case was probable.

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Etizolam is a thienodiazepine anxiolytic which is said to have lower dependence potential than other benzodiazepines. We report a case of etizolam dependence in a young male with social anxiety disorder and moderate depression. This case report highlights the fact that the same caution be exercised while prescribing etizolam with respect to its potential to cause dependence as with any other benzodiazepine.

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Objective: The curtailed knowledge about neonicotinoids that it has low affinity for vertebrate relative to insect nicotinic receptors is a major factor for its widespread use assuming that it is much safer than the previous generation insecticides. But literature regarding effect of thiamethoxam (second generation neonicotinoid)on immune system is not available. Also, there might be chances of interaction of heavy persistent metals in the water table with these pesticides. So, this study was undertaken with the objective to find immunotoxic alterations of lead acetate after exposure with thiamethoxam in animal model. Materials and Methods: For this albino mice were randomly divided into 6 groups (numbered I to VI) each containing 6 mice. Animals of groups I and II were administered 87.1 mg/kg b.w.( body weight) and 43.5 mg/kg b.w. respectively of thiamethoxam. Group III animals, lead acetate was administered orally and IV and V mice were administered combination of lead acetate and thiamethoxam at higher and lower dose level for 28 days. The group VI was control group. On 29 ^th day and humoral and cell mediated immune responses, TLC (Total leukocyte count), DLC (Differential leukocyte count), serum total protein, globulin and albumin, and histopathological studies were conducted. Result: The result obtained clearly indicated that on oral administration of thiamethoxam immunotoxicity was induced in mice in dose related manner. Lead acetate when administered for 28 days showed immunotoxic potential. Thiamethoxam and lead acetate when administered together did not lead to any new altered immunotoxic response but additive toxic effects of both were observed.

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Objectives: Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms in elderly men. Selective alfa ₁ -adrenergic antagonists are now first-line drugs in the medical management of BPH. We conducted a single-blind, parallel group, randomized, controlled trial to compare the effectiveness and safety of the new alfa ₁ -blocker silodosin versus the established drug tamsulosin in symptomatic BPH. Materials and Methods: Ambulatory male BPH patients, aged above 50 years, were recruited on the basis of International Prostate Symptom Score (IPSS). Subjects were randomized in 1:1 ratio to receive either tamsulosin 0.4 mg controlled release or silodosin 8 mg once daily after dinner for 12-week. Primary outcome measure was reduction in IPSS. Proportion of subjects who achieved IPSS <8, change in prostate size as assessed by ultrasonography and changes in peak urine flow rate and allied uroflowmetry parameters, were secondary effectiveness variables. Treatment emergent adverse events were recorded. Results: Data of 53 subjects - 26 on silodosin and 27 on tamsulosin were analyzed. Final IPSS at 12-week was significantly less than baseline for both groups. However, groups remained comparable in terms of IPSS at all visits. There was a significant impact on sexual function (assessed by IPSS sexual function score) in silodosin arm compared with tamsulosin. Prostate size and uroflowmetry parameters did not change. Both treatments were well-tolerated. Retrograde ejaculation was encountered only with silodosin and postural hypotension only with tamsulosin. Conclusions: Silodosin is comparable to tamsulosin in the treatment of BPH in Indian men. However, retrograde ejaculation may be troublesome for sexually active patients.

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Objectives: Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. Materials and Methods: We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. Results: The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). Conclusion: These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation.

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Introduction: L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats. Materials and Methods: Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique. Results: Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination. Conclusion: Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect.

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Objectives: Inflammation is one of the predictors of atrial fibrillation (AF) following surgical or interventional cardiac procedures. Recent evidence suggests that colchicine may represent a new strategy to prevent AF following cardiac procedures. This study aims to assess the antiinflammatory efficacy of colchicine in prevention of early AF event (EAFE). Materials and Methods: We reviewed all available studies that assessed the effectiveness of colchicine therapy on the occurrence of AF in patients undergoing cardiac procedures. Meta-analysis was performed by random effect inverse variance-weighted method by entering AF events and the total population from each study. Results: After thorough review of the databases, we found three studies comparing colchicine and placebo which had EAFE as the outcome. Of 584 patients, 286 patients were on colchicine and 298 on placebo. All the three studies were randomized. After pooled analysis, colchicine was associated with significant reduction in AF events compared to placebo (odds ratio = 0.44 [0.29, 0.66], P < 0.001). There was no statistical heterogeneity between included studies (χ² = 0.45, P = 0.80, I² = 0%). Conclusion: Colchicine may prove beneficial in the prevention of AF following cardiac surgery. Further research is warranted.

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Hyponatremia is a known adverse effect of duloxetine, and it can lead to potentially life-threatening complications. Administration of thiazide diuretics also has been the cause of hyponatremia. We report a case of duloxetine-induced hyponatremia in an elderly patient treated with thiazide diuretics. An 86-year-old woman treated with the trichlormethiazide was admitted for vertebral compression fracture with disorientation and nausea on the 6 ^th day of treatment with duloxetine. Laboratory findings revealed hyponatremia, hypo-osmolality, concentrated urine, and increased urine sodium. Syndrome of inappropriate antidiuretic hormone was considered, therefore, duloxetine, and trichlormethiazide was discontinued and treated with fluid restriction, furosemide and sodium chloride administered orally. Disorientation and nausea were improved after correction of hyponatremia. Health care practitioners should be aware of the possibility of duloxetine-induced hyponatremia, particularly in patients treated with thiazide diuretics.

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Objectives: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant drugs. The addition of low dose of 5-hydroxytryptamine type 2A enhances the therapeutic effect of SSRIs. The purpose of the present studies was to test the effects of combined treatment of a low dose of ketanserin (KET) and escitalopram (ESC) on behavioral anomalies occurring after olfactory bulbectomy (OBX). Materials and Methods: Chronic Depression was induced by OBX as shown in behavioral tests such as Open field, social interaction, and hyperemotionality tests. Acute and chronic treatment effect of KET, ESC, and combination was administered to the OBX rats. Results: Chronic (14 days) treatment with KET (1 mg/kg) or ESC (10 mg/kg) alleviated the behavioral anomalies of olfactory bulbectomized rats in modified open field exploration, social interaction, hyperemotionality.  When KET treatment was combined with ESC, a short duration regimen (7 days) was sufficient to reverse the bulbectomy-induced anomalies. Conclusion: The combination therapy as a likely strategy to achieve an early-onset of antidepressant action.

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Objectives: To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity. Materials and Methods : Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed. Results: Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments. Conclusion : Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection.

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Methotrexate (MTX) is one of the most commonly used medicines in the treatment of psoriatic arthritis. The drug can produce steatosis and cirrhosis. Autoimmune hepatitis is a rare and serious adverse effect. We describe the case of a 53-year-old woman who developed autoimmune hepatitis after a long-term use of MTX for psoriatic arthritis. Hepatitis was completely resolved 4 months after stopping this drug. The pathophysiologic mechanisms of a drug-induced autoimmunity are unclear and complex. This report confirms the need to monitor liver enzymes carefully in patients using long-term treatment with MTX for psoriasis or rheumatoid arthritis.

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Carbamazepine overdose usually presents with neurological manifestations such as ataxia, seizures and altered sensorium or cardiac manifestations that include tachycardia, hypotension and ventricular extra-systoles. We report a patient with carbamazepine overdose who manifested recurrent hypoglycemia on the third and fourth day following ingestion that resolved with supportive therapy.

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Venlafaxine is a serotonin-norepinephrine reuptake inhibitor used for the management of depression and anxiety disorders. The drug has been rarely reported to be associated with the development of akathisia. A review of the literature revealed only three such case reports. In this report we present the case of a middle-aged female, who developed akathisia while receiving venlafaxine (225 mg/day). The patient was suffering from recurrent depressive disorder and Crohn's disease. She was earlier treated with Cap venlafaxine up to 75 mg/day, but had a relapse of depressive symptoms when an attempt was made to taper off venlafaxine. When she presented to us, her depressive symptoms amounted to severe depression without psychotic symptoms. In view of the past response to venlafaxine, she was restarted on venlafaxine, but did not achieve remission of symptoms with the earlier dose and hence, venlafaxine was increased up to 225 mg/day. Within 48 h of increasing venlafaxine to 225 mg/day, she developed akathisia, which subsided after stopping venlafaxine.

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The need to revise the curriculum for the postgraduate course (M.D.) in Pharmacology has been perceived by the academicians in India since quite some time. The changing professional requirements of the graduating students, the current scenario vis a vis animal experimentation and the emphasis of the Medical Council of India on a competency based curriculum has triggered this felt need. In spite of the fact that most medical institutions and universities in India offer postgraduate courses in pharmacology, the curriculum lacks uniformity with extreme variations observed at some places. This article attempts to analyze the existing curricula in pharmacology in India and suggest modifications that could be recommended to the suitable regulatory bodies for implementation. A revision of objectives in the three domains of learning, development of skills that help develop suitable competencies, adoption of teaching learning methods in addition to the conventional methods, and a rethink on the assessment methods have been recommended. Development and validation of alternatives skill-based modules in lieu of animal experiments are recommended. Additional skills like medical writing and communication skills, professionalism and ethics, multi and inter-disciplinary integration and collaboration and a wider exposure of students to the pharmaceutical, academic, regulatory and research institutions for onsite learning were also recommended to fulfill their future career requirements.

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Objective: Neostigmine can produce analgesia by acting on the spinal cord. This study was to determine the optimal single-dose of epidural neostigmine for postoperative analgesia after partial hepatectomy. Patients and Methods: Twenty-six patients undergoing elective partial hepatectomy under general anesthesia combined with epidural block were studied. The dose of epidural neostigmine was determined using Dixon's up-and-down method, starting from neostigmine 100 μg with an interval of 25 μg. Thirty minutes after skin incision, a predetermined dose of neostigmine was injected via the epidural catheter. Each patient received 0.125% bupivacaine and fentanyl 2 μg/ml for patient controlled epidural analgesia (PCEA) after the operation. Assessment of analgesia quality was performed at 8 h and 24 h after the operation. Results : The ED ₅₀ of epidural neostigmine in combination with PCEA for satisfactory analgesia was 226.78 ± 33.20 μg. Probit analysis showed that the ED ₅₀ and ED ₉₅ of epidural neostigmine were 228.63 μg (95% CI = 197.95-299.77 μg) and 300.12 μg (95% CI = 259.44-741.65 μg), respectively. Conclusion: The ED ₅₀ and ED ₉₅ of epidural neostigmine in combination with PCEA for satisfactory analgesia after partial hepatectomy were 228.63 μg (95% CI = 197.95-299.77 μg) and 300.12 μg (95% CI = 259.44-741.65 μg).

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